This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: Primary Objectives The phase I component of this study will determine the MTD and DLT of escalating doses of erlotinib in combination with sirolimus, both administered on a continuous once daily dosing schedule to adult patients with malignant glioma, who are not receiving EIAED; The phase II component of this study will evaluate preliminary efficacy (response rate [RR], progression free survival [PFS] and overall survival [OS]) of erlotinib and sirolimus combination therapy in GBM/GS patients who are not undergoing surgery at the time of recurrence or relapse (dose expansion arm; Evaluate molecular determinants of response to this combination of erlotinib and sirolimus, especially the roles of the mutation of EGFR (vIII mutant and other somatic mutations of vIII and mutation/deletion of PTEN.